Membrane proteins control the flow of information, nutrients, and signals through the cell membrane, and are the targets for more than 40% of FDA-approved drugs. Monoclonal antibodies (MAbs) that target membrane proteins can be exceptionally useful in research, diagnostic, and therapeutic applications, but for most membrane proteins there are no MAbs that recognize the native protein on the cell surface. The need for such MAbs has been recognized by industry and the NIH, but efforts to identify such MAbs are limited by the difficulty in expressing and purifying membrane proteins in exogenous systems and by conventional MAb isolation strategies that typically focus on one target at a time. A novel approach to identify membrane protein MAbs in a high-throughput manner is needed to derive MAbs against the entire human membrane proteome. Here we propose a platform technology that can be used to rapidly isolate MAbs against structurally-intact membrane proteins for therapeutic development, diagnostics, and biomedical research.